Sulfite nematocides



United States Patent 3,428,734 SULFITE NEMATOCIDES Bogislav von Schmeling, Hamden, and Rupert A. Covey, Wolcott, Conn., assignors to Uniroyal, Inc., New York,

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These nematocides are considerably less costly and less phytotoxic than those previously known.

They have the generic formula:

N.Y., a corporation of New Jersey 1 s N 5 ROg-0R' N0 Drawing. Continuation-impart of app ication er. 0. t

532,685, Mar. 7, 1966. This application June 2, 1967, Where a1k.YnY1 grmP havng from 3 i" 12 carbon ser No 643 056 atoms, or a substituted alkynyl group wherein from 1 to s CL 424 11, 12 Claims 3 hydrogens are replaced by a halo group, particularly Int. Cl. A01n 9/14; C07c 143/00 10 a bromo or a chloro group; and R is a almphatic radical,

viz, an alkyl group having from 1 to 18 carbon atoms,

This invention relates to sulfite diesters and particpreferably f 6 to 12; an alkenyl group. having from ularly to their use for the control of parasitic nematodes. 3 to 18 capbon atoms, o an alkynyl rou or substituted This application is a continuation-in-part of our prior lk l group as defingd i R above, Additionally, R copending application filed Mall may be an alicyclic radical, viz., a cycloalkyl group hav- 1966, now abandoned. ing from 3 to 14 carbon atoms.

The Control Of nematodes is a difficult and l -lex R may also be a substituted aliphatic and alicyclic Problem of great economic importance in agriculture, radical. For example, the alkyl, alkenyl and cycloalkyl horticulture and forestry. See, U.S. Patent 3,112,244 for groups may contain one to six or more halo groups, pardetailed discussion of this problem. Several nematocidal 20 i l l hl o or bromo and the alkynyl group ma be chemicals are disclosed in the patent literature, e.g., U.S. b i d i h one t th e h l groups, particularly Patent 2,909,457 teaches thioethers, such as phenyl sul hl or b fids; Patent 2,938,831 Suggests dialkyl PY S/ Certain of the above compounds are new compositions Phosphofothioates; Patent 2,957,800 Shows amides of matter, namely, where 'R is an unsubstituted or halo- Of dihalopropionic acids; Patent 3,113,908 teaches substituted cycloalkyl, alkenyl or alkynyl group and R methyl isothiocyanates; U.S. Patent 3,086,907 illustrates i an alkynyi r halosu b imted alikynyl group, Additionfiv -me re h r y l n and lactams; and ally, the unsubstituted and halosulbstituted alkyl halo- U.S. Patent 3,112,244 teaches phosphorothioates d alkynyl sulfites have not been known materials. For these phosphorothioites. compounds the number of canbon atoms and the halo- In accordance with this invention a new class of nemsubstitutions are as defined above. atocides has been discoverd which are effective in con- Examples of the sulfites of the invention, and their trolling such parasitic nematodes as Meloidogyne spp. boiling points and sulfur analysis (where available) are and saprophytic forms such as Panagrellus redivivus. shown in the following tables:

TABLE A.ALKYNYL ALKYL SULFITES Sulfur Analysis Boiling Point,

P ar 1 eth l ulfit Piggargl lihyl sulfitefu 21.63 21.51 Propargyln-propy1su1fite 19.78 19.21 Propargyl isopropyl sulfite Propargy1n-buty1sulfite 18. 19 17.49 Propargyl1sobuty1su1fite- 18.19 17.85 Propargyl n-amyl sulfite. 16. 88 16. 85 Propargyl n-hexyl sulfite 15. 7 15.56 Propargyl n-heptyl sulfite 14. 67 14. 50 Propargyl n-octyl su1fite 13.78 13.89 Propargyl 2-oetyl sulfite... 13.78 13.18 Propargyl 2-ethy1hexyl sulfite 13.78 13.36 Propargyl 2,2,4-trimethylpenty1 sulfite 13. 78 13. 52 Propargyl n-nonyl sulfite 13. 03 12.78 Propargyl n-decyl sulfite 12.31 12.26 Propargy12-decy1 sulfite Propargyl n-undecyl sulfito 11.68 11.69 Propargyl 5-ethyl-2-nonyl sulfite. 11.68 11.38 Propargyl n-dodecyl su1fite 11.11 11.60 Propargyl 2-buty10etyl sulfite 11.11 10.63 Propargyl n-tridecyl sulfite. 10. 60 9. 89 Proparg'yl n-tetradeeyl sulfite 10.02 10.29 Propargyl n-hexadeeyl snlfite. 9. 32 9. 57 Propargyl n-octadecy1 sulfite... 8. 60 8. 87 2-(3-butynyl) isobutyl sulfite-.. 2-(3-butynyl) n-decyl sulfite. 11. 68 11. 2-(3-butynyl) n-hexadecyl sulfite. 1-(2-butynyl) n-octyl sulfite 1 (2-butynyl) trldecyl sulfite 10. 13 10. 24 2-methyl-2-(3-butynyl) n-decyl sulfite 11. 12 11. 93

1-(3-butynyl) n-oetyl sulfite 1-(3-hexynyl) n-hexyl sulfite. 1-(2-heptyny n-butyl sulfite 1-(3-nonynyl) n-hexyl sulfite. 1-(6dodecynyl) methyl sulfite TABLE B.-HALO-ALKYNYL ALKYL SULFITES Sulfur Analysis Bolling Point,

Calcd. Found TABLE C.ALKYNYL CYCLOALKYL SULFITES Propargyl cyclohexyl sulfite Prop-argyl 2.1nethyl cyclohexy Propargyl cyelooctyl sulfite Sulfur Analysis Boiling Point,

Calcd. Found 15. 81 16. 01 93-100 (0.04 mm.) 100-116 (0.5 mm.) Above 130 (0.25 mm.) 11. 28 10. 52

Propargyl Z-cyclohexyl-oyclohexyl sulfite Propargyl 4-t-butylcyolol1exyl sulfite Propargyl cyclopentyl sulfite 1-(2-butynyl) cyolohexyl sulfite 1-(4-chloro-2-butynyl) cyclohexyl sulfite. Propargyl 4-methylcyelohexyl'methyl sulfite TABLE D.-ALKYNYL HALOALKYL SULFITES Boiling Point,

TABLE E.ALKYNYL ALKYENYL SULFITES 78-82 (0.3 mIn.) 92-97 (0.2 mm.) Above 57 (1.0 mm.)

140-150 (1.8 n1m.) 108-112 (0.25 mm.)

Sulfur Analysis Calcd. Found Boiling Point,

Propargyl allyl sulfite Propargyl 1-(3-butenyl) sulfite. Propargyl l-(2-butenyl) sulfite Iropargyl 3,7-dimethyl-6-oetenyl sulfite. Propargyl 1-(3-hexenyl) sulfite Propargyl w'undecenyl sulfite 1-(4-chl0r0-2-butynyl) w-undecenyl sulfite (0.35 mm.) 123-132 (0.35 mm.)

2(3-bntynyl 1-(2-propenyl) sulfite TABLE F.DIALKYNYL SULFITES Boiling Point,

Sulfur Analysis Calcd. Found 'ifii""i%f5i" Sulfur Analysis Caled. Found Dipropargyl sulfite 105-108 (18 mm.) 1 Propargyl 2-(3-butynyl) sulfite 1-(4-chloro-2-butynyl) hexynyl sulfite. bis[1-(4-chl0ro-2-butynyD] sulfite bisl1-(2-butynyl)] sulfite The sulfate diesters may be conveniently prepared by reacting thionyl chloride with the appropriate alcohols:

ClQ-OR ROB. ROISIOR 1101 For details of this preparation see our US. Patent 3,179,684, the teaching of which is incorporated herein by reference.

The sulfite nematocide can be used together with solid carrier such as clay-type granules or as liquids in the form of emulsifiable concentrates. A typical emulsifiable concentrate would contain about 70% of the active compound, emulsifier and 15 solvent monochlorobenzene. Six pounds of such concentrate has a total volume of about one gallon and is diluted in water to give the desired amount of chemical per acre. Broadly, from 5 to 500 pounds of the sulfite should be applied per acre of soil, preferably, from to 250 pounds, depending on such conditions as the type of soil and degree of the infestation of the crop.

In the case of anthelmintic usage, the dosage is limited by the toxicity of the particular animal being treated. This may be determined by means of a conventional toxicity probe.

To show the elficacy of the compounds of the invention, the following test procedures were employed:

Nematocide testing methods The ability of the chemicals to control nematodes was evaluated by employing the following testing techniq es:

Procedure #1 (contact test) Three hundred milligrams chemical is dissolved in 10 ml. of acetone. Ninety milligrams (three drops from a standard medicine dropper) of this 3.0% solution is added to a BPI (Bureau of Plant Industry) standard watch glass containing 150 mg. of a 0.01% solution of Triton X- (five drops) in distilled water. Thirty milligrams (1 drop) of a nematode suspension containing 50-100 live Panagrellus redivivus nematodes is added to the watch glass containing the chemical preparation. The final concentration of chemical in the BPI Watch glass is 1.0% (10,000 p.p.m.). The test is conducted in duplicate using a dilution series. An untreated check, i.e. two watch glasses containing 0.01% Triton X-100 solution and nematodes but no chemical, is included in the test. The watch glasses are placed in 100 x 15 mm. inverted Petri plates and sealed with water to avoid evaporation. The test is kept in the laboratory at room temperature. The results are taken by microscopic inspection of the nematodes in the watch glasses. They are recorded as percent nematode control by contact after 48 hours.

Procedure #2 (fumigant test) One drop of a nematode suspension containing 50-100 live Panagrellus redivivus nematodes is placed in each of two BPI watch glasses. An additional drop of distilled water is added to the watch glasses to avoid drying out of the nematode culture. Thirty milligrams (1 drop) chemical is added to a third BPI Watch glass. This and the two watch glasses containing the nematodes are placed in an inverted Petri plate which is sealed with water. An untreated control, i.e. two watch glasses alone containing Procedure #3 (contact pot test) 250 milligrams of chemical is mixed with 60 mg. of wetting agent such as Atlox 6-2081 and suspended with 125 ml. distilled water. This chemical suspension is added to and manually mixed with 4.5 pounds of sandy soil severely infested with root-knot nematodes of the genus Meloidogyne. This amount of chemical is equivalent to a rate of 125 p.p.m. or 250 lbs./ acre based on the weight of an acre of soil 6" deep being 2,000,000 pounds. The treated 4.5 pounds of infested soil is filled into three fourinch post, placed on saucers in the greenhouse and watered by subirrigation. Three pots with infested soil but without the chemical treatment are included. Also included in the test are three 4" pots containing sterilized soil without a chemical treatment. Two weeks later a tomato seedling is planted in each treated and untreated pot. The test is kept in the greenhouse and watered regularly by subirrigation. Five weeks later the tomato roots are inspected for galls caused by the root-knot nematodes. The results are recorded in percent control.

In order to illustrate the instant invention the following examples are given:

EXAMPLE I The following table shows the results obtained with various alkyl propargyl sulfites, using test procedure #1:

TABLE I Percent control at p.p.m.

Alkyl Group R:

n-Propyl 17. 5 99. 5 n-Hexyl 3 100 100 n-OctyL. 78 100 100 n-Decyl 75 100 100 Dudecyl 97 100 100 The above table shows the marked effect of the alkyl alkynyl sulfites of the invention. In the case of the propargyl compounds, i.e., compounds wherein R is the higher molecular weight materials are more effective at low concentrations.

' EXAMPLE II The following are additional compounds which show 95% or higher control of the Panagrellus sp. at 10,000 ppm. in the contact test (Procedure #1) propargyl methyl sulfite propargyl ethyl sulfite propargyl isobutyl sulfite propargyl n-amyl sulfite propargyl n-heptyl sulfite propargyl Z-methylcyclohexyl sulfite propargyl 2-octyl sulfite propargyl 2-ethylhexyl sulfite propargyl iso octyl sulfite derived from the commercially available isooctyl alcohol (Enjay) and isodecylcellosolve (Union Carbide).

6 EXAMPLE 111 Again using test procedure #1, the following compounds were shown to be effective at the concentrations indicated:

Compound P.p.m. Percent control l-(4-chloro-2-butynyl) n-hexyl sulfite 100 100 1-(4-chloro-2-butynyl) methyl sulfite 100 1-(4-ch1oro-2-butynyl) n-decyl sulfite. 100 100 1-(4-chloro-2-butynyl) n-butyl sulfite 100 1-(4-chloro-2-butyuy1) m-undecenyl sulfite" 98 1-(4-chloro-2-butynyl) n-octyl sulfite 100 100 1-(4-chloro-2-butynyl) 2-chloroethyl sulfite 100 100 1-(4-chloro-2-butynyl) 3, 7-dimethyl-6, 7-dibromooctyl sulfite 1, 000 99 EXAMPLE IV The following results were obtained in the fumigant test (Procedure #2):

Propargyl iso octyl sulfite 100 Propargyl 2,2,4-trimethylpentyl sulfite 80 Propargyl 4-rnethylcyclohexylmethyl sulfite 100 Propargyl n-nonyl sulfite 100 2-(3-butynyl) isobutyl sulfite 100 Dipropargyl sulfite 100 Propargyl 1-(3-buteny1) sulfite 100 Propargyl 1-(3-hexenyl) sulfite 100 EXAMPLEV The following results were obtained in the pot test (Procedure #3) Percent control of root-knot nematodes Compound lbs/acre Propargyl namyl sulfite 100 Propargyl n-hexyl sulfite 100 Propargyl n-heptyl sulfite 100 Propargyl n-octyl sulfite 100 Propargy iso octyl sulfite 95 Propargyl 'i-methylcyclohexyl-methyl sulfite 100 95 Propargyl n-decyl sulfite 100 Propargyl n-dodecyl sulfite 83 Dipropargyl sulfite 100 94 Propargyl l-(3-hexenyl) sulfite 90 EXAMPLE VI The following example shows the effect of the compounds of the invention as anthelmintics in mice.

Anthelmintic screening test The Parasite: Nemotospiroides dubius-(Nemotode) larval stage.

The Host: Swiss-Webster male albino mice, 1822 gm.

body weight.

Route of infection: Oral-Gavage. Approximately 20 larvae per mouse, suspended in 0.5 ml. physiological saline.

Route of treatment: Oral-Gavage.

A. Toxicity probe: The compound was subjected to an oral toxicity probe. The purpose was to establish an oral dose level which, when introduced two times daily on two successive days, does not kill the 18-22 gm. male albino mice for 1 week.

Different mouse groups were instomated with 2,000, 1,000 and 500 mg./kg. body weight of each agent. The

concentrations of agent were delivered in 0.5 ml. to a 20 gm. mouse and the volume was increased or decreased depending on the body weight, so that the agentzbody weight ratio remained constant. The agents were suspended and homogenized in a methylcellulose vehicle.

B. Infections: Sixty male albino mice were infected with approximately 20 Nematospiroides dubius larvae each. The larvae were suspended in saline and stomach tubed in a volume of 0.5 ml. each. The mice were housed individually and on the 12th day after infection fecal pellets were collected from each mouse, individually. The pellets were incubated in Petri dishes on moist paper, at room temperature. On day 7 after infection, each dish was examined for larvae and it was established that 100% mouse infection had been achieved.

The test groups, comprised of mice per group, were as follows:

Infection control-infected; no treatment.

Vehicle controlinfected; treated exactly as the test group, except that only the methylcellulose vehicle was instomated.

Anthelmintic control-infected; treated twice daily, for one day with carbon tetrachloride at 2,000 mg./kg., in milk.

Test groupsinfected; treated twice daily for two consecutive days with the candidate compound.

The treatment, in all cases, commenced on the 14th day after infection. Fecal samples were collected on the 6th day after treatment commenced. This will have permitted enough time for flushing out of the parasites and residual eggs, if a compound is effective. The stools were incubated in Petri dishes on moist paper. Seven days later the plates were examined for larvae. The presence of larvae indicated the persistence of eggs and thus the failure of the compound to have destroyed or flushed out the parasite.

Results The oral toxicity probe suggested that the following concentrations of test compound could be used in the actual assay.

Estimated maximum Compound: tolerable dose, mg./kg. Propargyl dodecyl sulfite 200 The results of the drug assay are presented below in Table VI. All mice were established as having been infected prior to treatment.

TABLE VI The Effectiveness of Propargyl Dodecyl Sulfite Against N. dubius.

The carbon tetrachloride run serves as anthelmintic control and the methylcellulose as vehicle control. All of mice yielded larvae and exhibited parasites in the methylcellulose run. Neither larvae nor mature intestinal parasites were found in the propargyl dodecyl sulfite or the carbon tetrachloride run.

The above data show that the chemicals of the invention, as illustrated by the eifectiveness of propargyl dodecyl sulfite, are effective nematocides in animals.

Having thus described our invention, what we claim and desire to protect by Letters Patent is:

1. The method of controlling nematodes which comprises contacting nematodes with a mixted sulfite diester of an acyclic alkynyl alcohol and an aliphatic alcohol or cycloaliphatic alcohol.

2. The method of controlling nematodes which comprises contacting said nematodes with a compound represented by the formula:

in which R is an unsubstituted or halo-substituted alkyl, 2. cycloalkyl, alkenyl, or alkynyl group, and R is an alkynyl or halo-substituted alkynyl radical.

3. The method of claim 2 wherein the compound is a propargyl alkyl sulfite.

4. The method of claim 3 wherein the alkyl group has from 1 to 18 carbon atoms.

5. The method of claim 2 wherein the compound is a l-(2-butynyl) alkyl sulfite.

6. The method of claim 2 wherein the compound is propargyl n-decyl sulfite.

7. The method of claim 2 wherein the compound is propargyl n-octyl sulfite.

8. The method of claim 2 wherein the compound is bisropargyl sulfite.

9. The method of claim 2 wherein the compound is propargyl n-hexyl sulfite.

10. The method of claim 2 wherein the compound is propargyl n-dodecyl sulfite.

11. A compound having the formula:

wherein R is an unsubstituted or halosubstituted cycloalkyl, alkenyl or alkynyl group and R' is an alkynyl or halo-substituted alkynyl group.

12. A compound of the formula ROgOR wherein R is alkyl or haloalkyl and R' is haloalkynyl.

Each Times No. Surv. Percent Persisting Compound Dose, Daily Days Mice,

rug/kg. day Larvae 2 Parasite 5 Propargyl dodecyl sulfite. 200 2 2 3 0 0 Carbon tetrachloride 2,000 2 1 2 0 0 Methylcellulose. 2 2 4 100 Infection controL 3 100 100 Indicates number of mice surviving on the seventh day after treatment commenced. Fecal pellets were collected and cultured from each mouse and then the mice were autopsied. 2 The larvae column indicates the percentage of mice still shedding eggs which become larvae. The 100% figure indicates that all mice still produced eggs and hence the compound was inefiective under the conditions of this test.

3 The Parasite column indicates the percentage of mice which exhibited intestinal wonns,

mature, upon autopsy.

References Cited LEWIS GOTTS, Primary Examiner.

S. K. ROSE, Assistant Examiner.

US. Cl. X.R. 

1. THE METHOD OF CONTROLLING NEMATODES WHICH COMPRISES CONTACTING NEMATODES WITH A MIXTED SULFITE DIESTER OF AN ACYCLIC ALKYNYL ALCOHOL AND AN ALIPHATIC ALCOHOL OR CYCLOALIPHATIC ALCOHOL.
 12. A COMPOUND OF THE FORMULA 